The Expression of ILT4 in Myeloid Dendritic Cells in Patients with Hepatocellular Carcinoma

ABSTRACT

Immunoglobulin-like transcript (ILT) 4 is an inhibitory immune receptor of the immunoglobulin superfamily, which could deliver inhibitory signals and induce immunosuppression. The significance of the expression of ILT4 in mDCs subsets in patients with hepatocellular carcinoma (HCC) remains unclear. In this study, the frequency of mDCs subsets in the peripheral blood of 121 patients with HCC and 103 normal controls, and in the tumor and tumor free liver tissues (TFL) of 43 HCC patients was analyzed by flow cytometry. Then, the expressions of ILT4 in mDCs subsets in the microenvironment of liver cancer were also analyzed. Results showed that the percentage of CD1c⁺ subset was dramatically decreased in peripheral blood mononuclear cells (PBMCs) of HCC patients compared with normal controls, and also significantly decreased in tumor tissue compared with the TFL. The decreased of CD1c⁺ subset in blood could be a diagnostic factor for HCC with the area under the receiver operating characteristic curve 0.975 (P < 0.01). The percentage of ILT4⁺CD1c⁺ subset was dramatically increased in tumor than that of TFL and blood. There were significant correlations between the percentage of ILT4⁺ in CD1c⁺ subset in tumor and that of in blood. The percentage of ILT4⁺CD1c⁺ subset in tumor tissue was strongly associated with the Edmondson-Steiner stage in HCC (P = 0.03). Furthermore, the capacity of ILT4⁺CD1c⁺ subset producing IFN-γ was lower than ILT4⁻ CD1c subset in PBMC of HCC patients following Poly I:C stimulation. Taken together, the increased ILT4⁺CD1c⁺ subset in tumor tissue might play an important role in immune suppression for patients with HCC.

KEYWORDS:

• Myeloid dendritic cells
• CD1c⁺ subset
• ILT4
• hepatocellular carcinoma

Conflict of interest statement

The authors declared no competing interests in relation to the work described.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the local Ethics Committee of Nanjing Second Hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Funding

This work was supported by the Jiangsu Provincial Special Program of Medical Science [grant number BL2014005], and Medical Science and Technology Development Foundation, Nanjing Department of Health [grant number YKK16192 and YKK17167], and the Science and Technology Commission of Nanjing [grant number 201803001].